鞘内注射ω-芋螺毒素SO_3对神经痛大鼠脊髓Fos及Jun蛋白表达的影响

Effect of intrathecal ω-conopeptide SO_3 on expression of Fos and Jun protein in spinal cord of rats undergoing neuropathic pain

目的ω-芋螺毒素SO3是从海洋生物线纹芋螺中提取的一种多肽,为新型、特异性N型电压敏感性钙离子通道阻滞剂。通过研究鞘内注射ω-芋螺毒素SO3对坐骨神经慢性挤压伤(CCI模型)大鼠脊髓Fos、Jun蛋白表达的影响,探讨N型钙通道在伤害性信息传递中的作用。方法雄性SD大鼠72只,随机均分为9组,其中3组为假手术或单纯制作CCI模型后3、14d;3组为单次鞘内注射生理盐水或不同剂量SO3;另3组为持续鞘内注射生理盐水或不同剂量SO3共7d。在预定时间点,经左心室灌注4%多聚甲醛,取L4-L6段脊髓制备石蜡切片。用相应抗体行免疫组织化学染色,检测各组动物脊髓标本中Fos样或Jun样免疫反应阳性细胞的数量。结果大鼠CCI后脊髓背角Fos样或Jun样免疫反应阳性细胞数量显著升高;单次或持续鞘内注射生理盐水对其无明显影响;单次或持续鞘内注射SO3均可剂量依赖性抑制其上升。结论神经损伤后脊髓Fos、Jun蛋白表达增加,鞘内注射SO3可以减轻此种反应,提示N型钙通道阻滞剂在脊髓水平可以部分阻断伤害性信息传递。

AIM： To investigate the effect of intrathecal administration of ω-conopeptide SO3, a neotype Ntype calcium channel blocker, on the expression of Fos and Jun protein in the spinal cord of a rat model of chronic constriction injury （CCI）. METHODS： 72 male SD rats weighing 230 - 270 g were randomly divided into nine groups of 8 animals each. After i.t. NS or SO3 , the animals were perfused intracardially with 4% paraformaldehyde and the L4 - L6 spinal cord section was removed immediately. The changes of Fos and Jun protein expression in the spinal coM were detected by immunohistochemical techniques. RESULTS： The protein in the spinal cord was expression of Fos and Jun minimal in sham operation group; CCI induced significant increase in the expression of Fos and Jun protein in both the ipsilateral and the contralateral spinal cords. Acute or chronic i.t. NS had no effect on these expressions. Both acute or chronic i.t. SO3 significantly inhibited the increase in Fos and Jun protein expression induced by CCI in a dose-dependent manner. CONCLUSION： Upregulation of expression of Fos and Jun protein may be involved in the development of neuropathic pain, and i.t. SO3 inhibits the increased expression.